Дизайн, синтез і біологічне тестування N-фенілтієно[2,3-де]піримідин-4-амінів як інгібіторів FGFR1

Наша стаття, присвячена розробці нового класу інгібіторів протеїнкінази FGFR1, опублікована в журналі Bioorganic and Medicinal Chemistry.

Тези: Fibroblast grow factor receptor 1 (FGFR1) is an important anti-cancer target that plays crucial role in oncogenesis and oncogenic angiogenesis. The structure-activity relationship (SAR) of N-phenylthieno[2,3-d]pyrimidin-4-amines was investigated. Binding of active compounds with FGFR1 kinase was analyzed by molecular modeling studies. Selected active thieno[2,3-d]pyrimidines were tested for selectivity and antiproliferative activity. The most active compounds, 3-({6-phenylthieno[2,3-d]pyrimidin-4-yl}amino)phenol and 3-({5-phenylthieno[2,3-d]pyrimidin-4-yl}amino)phenol have IC₅₀ 0.16 and 0.18 μM, respectively. The results presented here may help to identify new thienopyrimidines with optimized cell growth inhibitory activity which may be further used as anticancer agents.     

• Design, synthesis and biological evaluation of N-phenylthieno[2,3-d]pyrimidin-4-amines as inhibitors of FGFR1. Gryshchenko AA, Bdzhola VG, Balanda AO, Briukhovetska NV, Kotey IM, Golub AG, Ruban TP, Lukash LL, Yarmoluk SM. Bioorg. Med. Chem. 2015, doi: 10.1016/j.bmc.2014.12.044.